Deferiprone increases endothelial nitric oxide synthase phosphorylation and nitric oxide production

Can J Physiol Pharmacol. 2018 Sep;96(9):879-885. doi: 10.1139/cjpp-2018-0012. Epub 2018 May 28.


Iron chelation can improve endothelial function. However, effect on endothelial function of deferiprone has not been reported. We hypothesized deferiprone could promote nitric oxide (NO) production in endothelial cells. We studied effects of deferiprone on blood nitrite and blood pressure after single oral dose (25 mg/kg) in healthy subjects and hemoglobin E/β-thalassemia patients. Further, effects of deferiprone on NO production and endothelial NO synthase (eNOS) phosphorylation in primary human pulmonary artery endothelial cells (HPAEC) were investigated in vitro. Blood nitrite levels were higher in patients with deferiprone therapy than those without deferiprone (P = 0.023, n = 16 each). Deferiprone increased nitrite in plasma and whole blood of healthy subjects (P = 0.002 and 0.044) and thalassemia patients (P = 0.003 and 0.046) at time 180 min (n = 20 each). Asymptomatic reduction in diastolic blood pressure (P = 0.005) and increase in heart rate (P = 0.009) were observed in healthy subjects, but not in thalassemia patients. In HPAEC, deferiprone increased cellular nitrite and phospho-eNOS (Ser1177) (P = 0.012 and 0.035, n = 6) without alteration in total eNOS protein and mRNA. We conclude that deferiprone can induce NO production by enhancing eNOS phosphorylation in endothelial cells.

Keywords: deferiprone; défériprone; endothelial nitric oxide synthase; nitric oxide; nitrite; nitrites; oxyde nitrique; oxyde nitrique synthase endothéliale; thalassemia; thalassémie.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Blood Pressure / drug effects
  • Deferiprone
  • Endothelial Cells / drug effects
  • Endothelial Cells / metabolism
  • Female
  • Humans
  • Male
  • Nitric Oxide / biosynthesis*
  • Nitric Oxide Synthase Type III / metabolism*
  • Phosphorylation / drug effects
  • Pyridones / pharmacology*
  • Thalassemia / metabolism
  • Thalassemia / pathology
  • Thalassemia / physiopathology


  • Pyridones
  • Deferiprone
  • Nitric Oxide
  • Nitric Oxide Synthase Type III